Ignite Creation Date:
2024-05-06 @ 3:28 AM
Last Modification Date:
2024-10-26 @ 11:34 AM
Study NCT ID:
NCT02292238
Status:
COMPLETED
Last Update Posted:
2022-06-28
First Post:
2014-11-10
Brief Title:
Benfotiamine in Alzheimers Disease A Pilot Study
Sponsor:
Burke Medical Research Institute
Organization:
Burke Medical Research Institute
Study Overview
Official Title:
Benfotiamine in Alzheimers Disease A Pilot Study
Status:
COMPLETED
Status Verified Date:
2022-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Benfotiamine
Brief Summary:
General Investigational Plan
Study Objectives The goal of this proposal is to determine whether enhancing brain glucose utilization minimizes cognitive decline in patients with Amnestic Mild Cognitive Impairment AMCI or mild Alzheimers disease AD dementia We propose a proof of concept double-blind placebo controlled pilot study to determine if increasing brain thiamine availability with the investigational new drug benfotiamine will minimize the decline in glucose utilization and slow the cognitive decline associated with the progression AMCIAD dementia
Specifically our objectives are two-fold
To test whether increasing brain thiamine by administering 600 mg per day 300 mgmorning and 300 mgevening of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimers Disease Assessment Scale ADAS-COG
To determine whether increasing brain thiamine availability with 600 mg 300 mgmorning and 300 mgevening per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission TomographyFGPET in the posterior cingulate
We will also carry out the following secondary objectives
Assess if there are differences in secondary clinical outcome measures NPI ADCSADL CDR Buschke between benfotiamine and placebo groups and whether specific cognitive domains ie activities of daily living learning and memory verbal memory behavioral etc are driving these changes
Compare ADAS-COG change scores in the benfotiamine and placebo groups within and between strata that were defined by initial cognitive impairment to attempt to identified the population that most benefits from benfotiamine
Compare changes in glucose utilization between the benfotiamine and placebo groups in secondary Regions of Interest ROIs including the hippocampus prefrontal regions and entorhinal cortex
Compare changes in whole brain glucose utilization between the benfotiamine and placebo groups using statistical parametric mapping SPM
Assess the correlation between changes in glucose utilization with changes in ADAS Cog
Determine if ApoE4 genotype alters the response to benfotiamine
Study Objectives The goal of this proposal is to determine whether enhancing brain glucose utilization minimizes cognitive decline in patients with Amnestic Mild Cognitive Impairment AMCI or mild Alzheimers disease AD dementia We propose a proof of concept double-blind placebo controlled pilot study to determine if increasing brain thiamine availability with the investigational new drug benfotiamine will minimize the decline in glucose utilization and slow the cognitive decline associated with the progression AMCIAD dementia
Specifically our objectives are two-fold
To test whether increasing brain thiamine by administering 600 mg per day 300 mgmorning and 300 mgevening of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimers Disease Assessment Scale ADAS-COG
To determine whether increasing brain thiamine availability with 600 mg 300 mgmorning and 300 mgevening per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission TomographyFGPET in the posterior cingulate
We will also carry out the following secondary objectives
Assess if there are differences in secondary clinical outcome measures NPI ADCSADL CDR Buschke between benfotiamine and placebo groups and whether specific cognitive domains ie activities of daily living learning and memory verbal memory behavioral etc are driving these changes
Compare ADAS-COG change scores in the benfotiamine and placebo groups within and between strata that were defined by initial cognitive impairment to attempt to identified the population that most benefits from benfotiamine
Compare changes in glucose utilization between the benfotiamine and placebo groups in secondary Regions of Interest ROIs including the hippocampus prefrontal regions and entorhinal cortex
Compare changes in whole brain glucose utilization between the benfotiamine and placebo groups using statistical parametric mapping SPM
Assess the correlation between changes in glucose utilization with changes in ADAS Cog
Determine if ApoE4 genotype alters the response to benfotiamine
Detailed Description:
Study Design
This study will be conducted at the Burke Rehabilitation Hospital under an IRB protocol Wplan to accrue a total of 76 male andor female patients 65 years with a diagnosis of AMCIAD dementia that are also amyloid positive by PET scan Patients will be randomized and blinded to either a benfotiamine or placebo group Because it is unknown whether there will be differential responses to treatment according to initial cognitive impairment participants will be stratified according to the median MMSE cut-off score of our historical METS population who are 65 years old and have an MMSE 21
In this double-blind study patients and their caregivers as well as all physicians clinicians coordinators and investigators interacting with the patients will be unaware of the treatment assignments Treatment assignments will be available to the safety-monitoring physician Dr Michael Reding who will have no unnecessary subject contact If necessary the code will be revealed to Dr Reding by the pharmacist Dr Thomas Grandville
Each patient will make six visits to the Memory Evaluation and Treatment Service METS clinic at Burke Rehabilitation Hospital Information on medication use vital signs outcome measures compliance and safetytolerability will be collected at each time point The screening visit visit 1 will take place within 30 days prior to baseline visit visit 2 Informed consentassent will be obtained from each subject or hisher caregiver prior to conducting any study related procedures During the screening visit a review of inclusionexclusion criteria will be completed along with the collection of demographic data disease history and information about prior and concomitant medications A complete medical history physical examination neurological examination including the MMSE CDR CSDD and vital signs will be collected Blood will be drawn to assess blood glucose Patients that are diagnosed as likely Alzheimer patients that are not hyperglycemic will then have an amyloid PET scan Only patients with a diagnosis of AD and a positive amyloid scan will be included Prior to baseline visit 2 FDGPET studies will be completed for each subject At the baseline visit visit 2 blood will be drawn to determine APOE and thiamine vitamin B1 status At visits 2-6 information on concomitant medications will be updated vitals will be taken medication compliance will be assessed and the following study measures will be administered Alzheimers Disease Assessment Scale ADASCog Buschke SRT Neuropsychological Inventory NPI Clinical Dementia Rating Scale CDR and Alzheimers Disease Cooperative Study-Activities of Daily Living ADCS-ADLs The final PET scan will be conducted approximately one week prior to the last visit In addition to safety assessments at time of each visit each patient will receive a call from the clinical coordinator at weeks 2 and 6 to assess for adverse events
The benfotiamine and placebo will be dispensed by the pharmacy at Burke under the direction of Thomas Grandville D Pharm The caregiver will administer the drug since patients with memory problems may forget to take it on a regular basis In the placebo group the active compound benfotiamine will be replaced with microcrystalline cellulose The other components shape and color are identical to the treatment Caregivers will be instructed to oversee the administration of the study medication as prescribed to ensure compliance A record of the number of capsules dispensed number returned and actual number taken will be recorded at scheduled visits Each patient will be treated for 12 months
The study cognitive measures include the ADAS-Cog our primary outcome measure Alzheimers Disease Cooperative Study-Activities of Daily Living Neuropsychiatric Inventory Clinical Dementia Rating Scale Buschke Selective Reminding Test SRT is a standard diagnostic tool in the assessment of verbal memory The BiologicalMechanistic Outcome Measures will be FDG-PET Scanning Procedures
Data Analysis Preliminary analyses will be conducted to describe the study sample and to confirm the relationship between level of glucose utilization and severity of cognitive impairment For continuous variables eg cognitive function glucose utilization we will first examine distributions to assess normality assumptions We will perform transformations as needed to stabilize the variance and to reduce skewness and kurtosis We will use means sd and proportions n to characterize the study sample T-tests and Chi-square or Wilcoxon rank sum test and Fisher where appropriate will be used to assess for any differences in patient characteristics according to treatment group We will use spearman correlation coefficients and linear regression unadjusted and adjusted for covariates to assess the relationship between FDG-PET and MMSE in the whole population as well as in MMSE stratified groups to examine the relationship between initial MMSE score and glucose uptake
All analyses to test study hypotheses will be run as intention to treat ITT Missing observations will be addressed by using the method of last observation carried forward LOCF
This study will be conducted at the Burke Rehabilitation Hospital under an IRB protocol Wplan to accrue a total of 76 male andor female patients 65 years with a diagnosis of AMCIAD dementia that are also amyloid positive by PET scan Patients will be randomized and blinded to either a benfotiamine or placebo group Because it is unknown whether there will be differential responses to treatment according to initial cognitive impairment participants will be stratified according to the median MMSE cut-off score of our historical METS population who are 65 years old and have an MMSE 21
In this double-blind study patients and their caregivers as well as all physicians clinicians coordinators and investigators interacting with the patients will be unaware of the treatment assignments Treatment assignments will be available to the safety-monitoring physician Dr Michael Reding who will have no unnecessary subject contact If necessary the code will be revealed to Dr Reding by the pharmacist Dr Thomas Grandville
Each patient will make six visits to the Memory Evaluation and Treatment Service METS clinic at Burke Rehabilitation Hospital Information on medication use vital signs outcome measures compliance and safetytolerability will be collected at each time point The screening visit visit 1 will take place within 30 days prior to baseline visit visit 2 Informed consentassent will be obtained from each subject or hisher caregiver prior to conducting any study related procedures During the screening visit a review of inclusionexclusion criteria will be completed along with the collection of demographic data disease history and information about prior and concomitant medications A complete medical history physical examination neurological examination including the MMSE CDR CSDD and vital signs will be collected Blood will be drawn to assess blood glucose Patients that are diagnosed as likely Alzheimer patients that are not hyperglycemic will then have an amyloid PET scan Only patients with a diagnosis of AD and a positive amyloid scan will be included Prior to baseline visit 2 FDGPET studies will be completed for each subject At the baseline visit visit 2 blood will be drawn to determine APOE and thiamine vitamin B1 status At visits 2-6 information on concomitant medications will be updated vitals will be taken medication compliance will be assessed and the following study measures will be administered Alzheimers Disease Assessment Scale ADASCog Buschke SRT Neuropsychological Inventory NPI Clinical Dementia Rating Scale CDR and Alzheimers Disease Cooperative Study-Activities of Daily Living ADCS-ADLs The final PET scan will be conducted approximately one week prior to the last visit In addition to safety assessments at time of each visit each patient will receive a call from the clinical coordinator at weeks 2 and 6 to assess for adverse events
The benfotiamine and placebo will be dispensed by the pharmacy at Burke under the direction of Thomas Grandville D Pharm The caregiver will administer the drug since patients with memory problems may forget to take it on a regular basis In the placebo group the active compound benfotiamine will be replaced with microcrystalline cellulose The other components shape and color are identical to the treatment Caregivers will be instructed to oversee the administration of the study medication as prescribed to ensure compliance A record of the number of capsules dispensed number returned and actual number taken will be recorded at scheduled visits Each patient will be treated for 12 months
The study cognitive measures include the ADAS-Cog our primary outcome measure Alzheimers Disease Cooperative Study-Activities of Daily Living Neuropsychiatric Inventory Clinical Dementia Rating Scale Buschke Selective Reminding Test SRT is a standard diagnostic tool in the assessment of verbal memory The BiologicalMechanistic Outcome Measures will be FDG-PET Scanning Procedures
Data Analysis Preliminary analyses will be conducted to describe the study sample and to confirm the relationship between level of glucose utilization and severity of cognitive impairment For continuous variables eg cognitive function glucose utilization we will first examine distributions to assess normality assumptions We will perform transformations as needed to stabilize the variance and to reduce skewness and kurtosis We will use means sd and proportions n to characterize the study sample T-tests and Chi-square or Wilcoxon rank sum test and Fisher where appropriate will be used to assess for any differences in patient characteristics according to treatment group We will use spearman correlation coefficients and linear regression unadjusted and adjusted for covariates to assess the relationship between FDG-PET and MMSE in the whole population as well as in MMSE stratified groups to examine the relationship between initial MMSE score and glucose uptake
All analyses to test study hypotheses will be run as intention to treat ITT Missing observations will be addressed by using the method of last observation carried forward LOCF
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1R01AG043679-01A1 | NIH | None | httpsreporternihgovquickSearch1R01AG043679-01A1 |